Incorporating labile bonds inside polymer backbone and side chains yields interesting polymer materials that are responsive to change of environmental stimuli. Drugs can be conjugated to various polymers through different conjugation linkages and spacers. One of the key factors influencing the release profile of conjugated drugs is the hydrolytic stability of the conjugated linkage. Generally, the hydrolysis of acid-labile linkages, including acetal, imine, hydrazone, and to some extent β-thiopropionate, are relatively fast and the conjugated drug can be completely released in the range of several hours to a few days. The cleavage of ester linkages are usually slow, which is beneficial for continuous and prolonged release. Another key structural factor is the water solubility of polymer–drug conjugates. Generally, the release rate from highly water-soluble prodrugs is fast. In prodrugs with large hydrophobic segments, the hydrophobic drugs are usually located in the hydrophobic core of micelles and nanoparticles, which limits the access to the water, hence lowering significantly the hydrolysis rate. Finally, self-immolative polymers are also an intriguing new class of materials. New synthetic pathways are needed to overcome the fact that much of the small molecules produced upon degradation are not active molecules useful for biomedical applications.

中文翻译：

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设计智能聚合物共轭物以控制释放有效载荷

在聚合物主链和侧链中掺入不稳定键会产生有趣的聚合物材料，这些材料可响应环境刺激的变化。药物可以通过不同的偶联键和间隔基与各种聚合物偶联。影响缀合药物释放曲线的关键因素之一是缀合键的水解稳定性。通常，酸不稳定键，包括乙缩醛，亚胺，，以及在一定程度上β-硫代丙酸酯的水解相对较快，并且缀合的药物可以在数小时至数天的范围内完全释放。酯键的裂解通常很慢，这有利于连续和延长释放。另一个关键的结构因素是聚合物-药物结合物的水溶性。一般来说，高水溶性前药的释放速度很快。在具有大疏水链段的前药中，疏水药物通常位于胶束和纳米颗粒的疏水核中，这限制了对水的获取，因此大大降低了水解速率。最后，自焚聚合物也是一种引人入胜的新型材料。需要新的合成途径来克服以下事实：降解时产生的许多小分子不是可用于生物医学应用的活性分子。自焚聚合物也是一种引人入胜的新型材料。需要新的合成途径来克服以下事实：降解时产生的许多小分子不是可用于生物医学应用的活性分子。自焚聚合物也是一种引人入胜的新型材料。需要新的合成途径来克服以下事实：降解时产生的许多小分子不是可用于生物医学应用的活性分子。